Neuroendocrine Division, Moffitt Cancer Center, Tampa, Florida.
Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan.
Clin Cancer Res. 2020 May 1;26(9):2124-2130. doi: 10.1158/1078-0432.CCR-19-3014. Epub 2020 Jan 24.
KEYNOTE-158 (ClinicalTrials.gov identifier: NCT02628067) investigated the efficacy and safety of pembrolizumab across multiple cancers. We present results from patients with previously treated advanced well-differentiated neuroendocrine tumors (NET).
Pembrolizumab 200 mg was administered every 3 weeks for 2 years or until progression, intolerable toxicity, or physician/patient decision. Tumor imaging was performed every 9 weeks for the first year and then every 12 weeks. Endpoints included objective response rate (ORR) per RECIST v1.1 by independent central radiologic review (primary) and duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety (secondary).
A total of 107 patients with NETs of the lung, appendix, small intestine, colon, rectum, or pancreas were treated. Median age was 59.0 years (range, 29-80), 44.9% had ECOG performance status 1, 40.2% had received ≥3 prior therapies for advanced disease, and 15.9% had PD-L1-positive tumors (combined positive score ≥1). Median follow-up was 24.2 months (range, 0.6-33.4). ORR was 3.7% (95% CI, 1.0-9.3), with zero complete responses and four partial responses (three pancreatic and one rectal) all in patients with PD-L1-negative tumors. Median DOR was not reached, with one of four responses ongoing after ≥21 months follow-up. Median PFS was 4.1 months (95% CI, 3.5-5.4); the 6-month PFS rate was 39.3%. Median OS was 24.2 months (95% CI, 15.8-32.5). Treatment-related adverse events (AE) occurred in 75.7% of patients, 21.5% of whom had grade 3-5 AEs.
Pembrolizumab monotherapy showed limited antitumor activity and manageable safety in patients with previously treated advanced well-differentiated NETs.
KEYNOTE-158（临床试验.gov 标识符：NCT02628067）研究了 pembrolizumab 在多种癌症中的疗效和安全性。我们报告了先前治疗过的晚期高分化神经内分泌肿瘤（NET）患者的结果。
pembrolizumab 200mg 每 3 周给药一次，持续 2 年或直至疾病进展、无法耐受的毒性或医生/患者决定。在第一年每 9 周进行一次肿瘤影像学检查，然后每 12 周进行一次。主要终点包括独立中央放射学审查（主要终点）的 RECIST v1.1 缓解率（ORR）和缓解持续时间（DOR）、无进展生存期（PFS）、总生存期（OS）和安全性（次要终点）。
共治疗了 107 例肺、阑尾、小肠、结肠、直肠或胰腺神经内分泌肿瘤患者。中位年龄为 59.0 岁（范围，29-80 岁），44.9%的患者 ECOG 表现状态为 1，40.2%的患者在晚期疾病中接受了≥3 种既往治疗，15.9%的患者肿瘤 PD-L1 阳性（联合阳性评分≥1）。中位随访时间为 24.2 个月（范围，0.6-33.4）。ORR 为 3.7%（95%CI，1.0-9.3），零例完全缓解，4 例部分缓解（3 例胰腺和 1 例直肠）均发生在 PD-L1 阴性肿瘤患者中。中位 DOR 未达到，4 例缓解中有 1 例在≥21 个月随访后仍持续。中位 PFS 为 4.1 个月（95%CI，3.5-5.4）；6 个月的 PFS 率为 39.3%。中位 OS 为 24.2 个月（95%CI，15.8-32.5）。75.7%的患者发生治疗相关不良事件（AE），其中 21.5%的患者发生 3-5 级 AE。
pembrolizumab 单药治疗在先前治疗过的晚期高分化 NET 患者中显示出有限的抗肿瘤活性和可管理的安全性。
